Computational studies on carbohydrates: in vacuo studies using a revised AMBER force field, AMB99C, designed for alpha-(1-->4) linkages

Abstract

Modifications to the AMBER force field [W.D. Cornell, P. Cieplak, C.I. Bayly, I.R. Gould, K. Merz, D.M. Ferguson, D.C. Spellmeyer, T. Fox, J.W. Caldwell, P.A. Kollman, J. Am. Chem. Soc., 117 (1995) 5179-5197] have been made to improve our ability to reproduce observed molecular properties of alpha-linked carbohydrates when calculated using empirical potential-energy functions. Molecular structures and energies obtained using gradient-optimized density functional methods with ab initio basis sets (B3LYP/6-31G*) on ten minimum-energy conformations of maltose [F.A. Momany, J.L. Willett, J. Comp. Chem., submitted for publication] were used to refine the empirical potentials. Molecular dynamics simulations on beta-maltose (i.e., the beta anomer of maltose), cyclohexamylose (alpha-cyclodextrin), cycloheptamylose (beta-cyclodextrin) and larger cyclomaltooligosaccharide structures were carried out and compared with experimental structural studies to test the new potentials. Ring-puckering potential during dynamics as well as conformational transitions to 'flipped' structures were examined. Results of the tests described here suggest that the revised AMBER parameters (AMB99C) are very good for computational studies of alpha-(1-->4)-linked carbohydrates.